Breast Cancer Management – Recent Advances
By:  CH Yip, Professor, Department of Surgery, University Malaya Medical Centre, Kuala Lumpur
Date: Aug 2003

Immediate Breast Reconstruction?

Recent techniques of skin sparing mastectomy with immediate breast reconstruction have shown no detrimental effect on disease-free or overall survival.  Immediate breast reconstruction gives better cosmetic results compared to delayed reconstruction, and there is less depression post-operatively.  

Molecular Markers

In recent years there has been an explosion in various molecular markers which may be prognostic or predictive.  Apart from the well-established estrogen and progesterone receptors, the one most studied in HER2-neu.  Over-expression of HER2-neu occurs in 20-30% of breast cancers, and is correlated to a poorer prognosis.  There are also some small studies which suggest a resistance to CMF chemotherapy and tamoxifen in cancers which over-express HER2-neu.  The most important advance in HER2 is the development of a monoclonal antibody to HER2, known as Herceptin, which can be used to treat metastatic breast cancers which over-express HER2.

Adjuvant Chemotherapy

Recent advances in the management of breast cancer has been in the field of adjuvant therapy.  The indications for the use of adjuvant chemotherapy has changed over the past 10 years, and currently almost all patients seem to require chemotherapy.

Apart from the node positive patients, who should be given adjuvant chemotherapy as long as they are fit, adjuvant chemotherapy is now advised for node negative patients, even if the tumour is less than 2 cm, especially if they are ER (estrogen receptor) negative or Grade 2-3.  The chemotherapy regimes used have also evolved over time, from the CMF (cyclophosphamide, methotrexate and 5-fluorouracil) regime that was the original chemotherapy regime used in Bonnadonna’s study, to the anthracycline-based  regimes, (such as AC, FAC or FEC)  and the current fad seem to be the regimes incorporating the taxanes, and recently the dose-dense regimes, utilizing a 2-weekly cycle instead of a 3-weekly cycles. 

Which then is the best regime, given the confusing data from so many studies, all claiming to give the best results?  Most consensus currently advise anthracycline based regimes, and the role of taxanes in adjuvant chemotherapy remain investigational, although the latest regime using Taxotere, Adriamycin and Cyclophosphamide (TAC) in the short-term analysis appears to give superior results compared to the anthracycline based regimes.

Adjuvant Hormone Therapy

Adjuvant hormone therapy with Tamoxifen 20 mg daily for 5 years is indicated for all ER (Estrogen receptor) positive or PR (progesterone receptor) positive patients, whatever the age.  For ER and PR negative patients, there is no benefit to giving tamoxifen, whatever the age.

A recent study using Arimidex (an aromatase inhibitor) as adjuvant hormone therapy in ER positive post-menopausal patients has shown a small but significant improvement in disease-free survival compared to Tamoxifen.  However this needs further assessment – perhaps the suggestion that cancers that overexpress HER2-neu may be resistant to Tamoxifen may lead to Arimidex being used in ER positive cancers that over-express HER2-neu, but as yet, there is absolutely no evidence to support this strategy.  Another recent strategy to induce a menopause in ER positive premenopausal patients with Zoladex for 2 years, have shown a survival benefit, although there is again not enough evidence to justify this approach.

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